Effects of hypernatremia on organic brain osmoles.

We studied the effects of varying degrees and durations of hypernatremia on the brain concentrations of organic compounds believed to be important, so-called "idiogenic" osmoles in rats by means of conventional biochemical assays, nuclear magnetic resonance spectroscopy, and high-performance liquid chromatography. There were no changes in the concentrations of these osmoles (specifically myoinositol, sorbitol, betaine, glycerophosphorylcholine [GPC], phosphocreatine, glutamine, glutamate, and taurine) in rats with acute (2 h) hypernatremia (serum Na 194 +/- 5 meq/liter). With severe (serum Na 180 +/- 4 meq/liter) chronic (7 d) hypernatremia, the concentrations of each of these osmoles except sorbitol increased significantly: myoinositol (65%), betaine (54%), GPC (132%), phosphocreatine (73%), glutamine (143%), glutamate (84%), taurine (78%), and urea (191%). Together, these changes account for 35% of the change in total brain osmolality. With moderate (serum Na 159 +/- 3 meq/liter) hypernatremia, more modest but significant increases in the concentrations of each of these osmoles except betaine and sorbitol were noted. When rats with severe chronic hypernatremia were allowed to drink water freely, their serum sodium as well as the brain concentrations of all of these organic osmoles except myoinositol returned to normal within 2 d. It is concluded that: idiogenic osmoles play an important role in osmoregulation in the brain of rats subjected to hypernatremia; the development of these substances occur more slowly than changes in serum sodium; and the decrease in concentration of myoinositol occurs significantly more slowly than the decrease in serum sodium which occurs when animals are allowed free access to water. These observations may be relevant to the clinical management of patients with hypernatremia.

[1]  S. Gullans,et al.  Characterization of the major brain osmolytes that accumulate in salt-loaded rats. , 1989, The American journal of physiology.

[2]  R. Balaban,et al.  A simple HPLC method for quantitating major organic solutes of renal medulla. , 1989, The American journal of physiology.

[3]  W. Guder,et al.  Regulation of organic osmolyte concentrations in tubules from rat renal inner medulla. , 1989, The American journal of physiology.

[4]  S. Gullans,et al.  Accumulation of major organic osmolytes in rat renal inner medulla in dehydration. , 1988, The American journal of physiology.

[5]  J. Lohr,et al.  Effect of acute and chronic hypernatremia on myoinositol and sorbitol concentration in rat brain and kidney. , 1988, Life sciences.

[6]  G. Somero.  Protons, osmolytes, and fitness of internal milieu for protein function. , 1986, The American journal of physiology.

[7]  R. Balaban,et al.  Predominant osmotically active organic solutes in rat and rabbit renal medullas. , 1986, The Journal of biological chemistry.

[8]  R. Balaban,et al.  Nitrogen-14 nuclear magnetic resonance spectroscopy of mammalian tissues. , 1983, The American journal of physiology.

[9]  M. E. Clark,et al.  Living with water stress: evolution of osmolyte systems. , 1982, Science.

[10]  D. Tuma,et al.  [14] Determinationof choline, phosphorylcholine, and betaine , 1981 .

[11]  A. Arieff,et al.  Abnormalities of cell volume regulation and their functional consequences. , 1980, The American journal of physiology.

[12]  J. Fleiss,et al.  Some Statistical Methods Useful in Circulation Research , 1980, Circulation research.

[13]  J. Dirgo,et al.  Taurine: a role in osmotic regulation of mammalian brain and possible clinical significance. , 1980, Life sciences.

[14]  P. Chan,et al.  Elevation of rat brain amino acids, ammonia and idiogenic osmoles induced by hyperosmolality , 1979, Brain Research.

[15]  M. Takayama,et al.  A new enzymatic method for determination of serum choline-containing phospholipids. , 1977, Clinica chimica acta; international journal of clinical chemistry.

[16]  A. Lockwood.  Acute and chronic hyperosmolality. Effects on cerebral amino acids and energy metabolism. , 1975, Archives of neurology.

[17]  L. Finberg.  Hypernatremic (hypertonic) dehydration in infants. , 1973, The New England journal of medicine.

[18]  A. Arieff,et al.  Studies on mechanisms of cerebral edema in diabetic comas. Effects of hyperglycemia and rapid lowering of plasma glucose in normal rabbits. , 1973, The Journal of clinical investigation.

[19]  E. H. Blaine,et al.  Renin Release after Hemorrhage and after Suprarenal Aortic Constriction in Dogs without Sodium Delivery to the Macula Densa , 1970, Circulation research.

[20]  J. Harrah,et al.  Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia. , 1968, The Journal of clinical investigation.

[21]  M. Witanowski.  Nitrogen-14 nuclear magnetic resonance—V1–4 , 1967 .

[22]  N. Talbot,et al.  STUDIES IN EXPERIMENTAL HYPERTONICITY I. Pathogenesis of the Clinical Syndrome, Biochemical Abnormalities and Cause of Death , 1960 .

[23]  K. Ullrich,et al.  [Occurrence of phosphorus compounds in various kidney sections and changes of their concentration in relation to diuretic conditions]. , 1956, Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere.

[24]  A. V. Wolf,et al.  Osmotic volumes of distribution; idiogenic changes in osmotic pressure associated with administration of hypertonic solutions. , 1955, The American journal of physiology.